Association of Apolipoprotein E Gene Polymorphism With Ischemic Stroke Involving Large-Vessel Disease and Its Relation to Serum Lipid Levels

A relationship between apolipoprotein E (Apo E) genotype and stroke was previously suggested, but with inconsistent results. We investigated the relationships among serum lipid levels, Apo E alleles and genotypes, and stroke risk factors in 216 stroke patients and 282 age- and sex-matched controls. Fasting blood samples were collected for total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride level determination and for genomic DNA extraction. Apo ϵ was genotyped by polymerase chain reaction–restriction fragment length polymorphism (Cfo I) analysis. Increasing levels of total cholesterol, LDL-C, HDL-C, and triglycerides were associated with elevated stroke risk and was more pronounced in Apo E4-carrying subjects than in E3- and/or E2-carrying subjects. Apo ϵ3 was significantly lower (0.546 vs 0.736; P < .001), whereas Apo ϵ4 was higher in the stroke patients (0.370 vs 0.181; P < .001); Apo ϵ2 was present at low but comparable frequencies. The prevalence of E3/E3 was lower and that of E4-containing phenotypes (E3/E4 and homozygous E4/E4) was higher in the stroke patients. The prevalence of the E4-containing phenotypes were significantly higher in ischemic versus hemorrhagic (P < .001) and in small-vessel versus large-vessel stroke cases (P < .001), and was associated with increased need for statin drugs (P = .040). Logistic regression models, after adjusting for potentially confounding variables including lipid profile, age, and sex, showed an significant association of apo ϵ4 genotype with risk of stroke (P = .033). Our findings indicate that Apo ϵ4 is an independent risk factor associated with an altered lipid profile in this study population.